HDL is highly heterogeneous and certain subfractions of HDL may be more specific markers of CHD risk. ApoA-I and apoA-II are the two major apolipoproteins associated with HDL. The two major classes of HDL particles include those containing only apoA-I (LpA-I) and those containing both apoA-I and apoA-II (LpA-I:A-II). LpA-I, but not LpA-I:A- II, has been found to be specifically associated with risk of premature CHD, and therefore it is important to determine the factors that influence the plasma levels of LpA-I. We have previously established that the most important metabolic determinant of plasma LpA-I levels is the rate of LpA-I catabolism. In order to further investigate LpA-I metabolism, we developed a method to preparatively isolate the three major subpopulations of LpA-I based on particle size. These three subclasses (Large, Medium, and Small) have different lipid and apolipoprotein composition and different levels of CETP and LCAT activity, indicative of different metabolic roles. Women have significantly higher levels than men of the Large LpA-I, but not of the Medium or Small particles. We investigated the in vivo metabolism of these LpA-I subclasses and determined that the Small LpA-I particles are more rapidly catabolized than the Large and Medium particles. This is the first direct demonstration that the size of an HDL particle affects its catabolic rate. Ongoing studies are directed toward investigating the mechanism by which particle size affects LpA-I catabolism. These studies included subjects of age 19 to 47 years. 52% of the study subjects were women, seven were East Asian, and three were East Indian.